How informed is informed consent and does it matter much, or as much as medical ethicists say it does? Do doctors have a duty only to make sure that their message is sent, or also a duty to make sure that it is received, and if received that it is retained? The prayer of General Absolution in the Book of Common Prayer refers to those things which we have done and ought not to have done, and those things which we ought to have done and have not done. When it comes to informed consent, there are also those things which patients have heard and ought not to have heard, and those things which they ought to have heard and have not.
This is proven in a recent paper in the British Medical Journal. Patients with stable angina in ten hospitals in the United States were asked what they thought the benefits were of the percutaneous coronary procedures they were about to undergo. The scientific evidence on this matter is more or less universally accepted: such procedures improve angina symptoms but do not increase life expectancy or reduce the rate of heart attacks.
One of the more extraordinary experiences of my medical career was injecting rural African women with a long-term contraceptive in a Catholic mission hospital under a portrait of Pope Paul VI. The contraceptive was handed to me by an aged Swiss nun who was otherwise deeply orthodox, but who recognized that worn-out women who had already had ten children were in danger of their lives if they had any more. I refrained from remarking on the paradox: I had already learned that there is more to life than intellectual consistency.
In the west, of course, the problem of unwanted pregnancy is different: it arises mainly among teenagers of what used to be called the lower classes. Pregnancy rates among the latter in the United States are among the highest in the western world. According to a paper in a recent edition of the New England Journal of Medicine, such pregnancies cost the United States $10 billion a year: to me a suspiciously round figure, especially as it includes the cost of education foregone by the pregnant girls. Perhaps I am a cynic, but I am not altogether so sanguine about the economic value of modern education. Be that as it may, the Centers for Disease Control and Prevention (CDC) has set a goal of reducing teenage pregnancy by 20 percent between 2009 and 2015.
An experiment conducted in St Louis provided 1404 girls aged between 14 and 19 with free contraceptive advice and free long-acting contraceptive devices to see whether such provision would reduce the rate of unwanted pregnancy among them. The comparison group was that of similar girls in the rest of the United States who were not included in the experiment.
We live in the age of acronym. To read a medical journal is sometimes like trying to decipher a code; once, when I was a judge in a competition of medical poetry, I read a poem composed entirely of figures and acronyms:
RTA [road traffic accident]
ETA [expected time of arrival] 13.20 hrs
CGS [Glasgow Coma Scale] 3…
The last line of the poem, inevitably, was:
Sometimes one has the impression that the acronym has been devised before the thing that it is attached to has been decided. In a recent paper in the New England Journal of Medicine, for example, I came across the acronym SWEDEHEART. It stood for the Swedish Web System for Enhancement and Development of Evidence-based Care in Heart Disease Evaluated According to Recommended Therapies. If the web system come before the acronym, however, you could see why the latter was necessary, the former being longer than the average tin-pot dictator’s list of honorific titles.
The paper in which the acronym occurred was yet another in which a common medical practice was shown to be valueless, or very nearly so. It turns out yet again that doctors do things not because they do the patients any good, but because they can do them.
When Hamlet tells Claudius that Polonius, whom he has just killed, is at dinner being eaten rather than eating, Claudius is puzzled. Hamlet explains that the worms are eating Polonius, and Claudius, still puzzled, asks Hamlet what he means by this
Nothing [replied Hamlet] but to show how a king may go a progress through the guts of a beggar.
In other words, we all come to the same end.
I thought of this passage when I read a paper about the death of Richard III in a recent edition of the Lancet. His remains were found recently buried under a car park in Leicester, a dismal provincial town in England, one of many ruined by planned modernization. The car park had once been a priory.
A long historical battle has raged over Richard’s real nature, whether he was hero or villain as per Shakespeare (few people think he might have been something in between the two). Certainly his remains, now more than 500 years old, have not been treated with undue respect: a team of forensic pathologists and archaeologists have examined them minutely for clues as to how he died at the battle of Bosworth Field in 1485.
The question is important because public health emergencies allow governments to ignore the usual restrictions or restraints upon their actions. In public health emergencies, governments can override property rights and abrogate all kinds of civil liberties such as freedom of movement. They can .r our goods and tells us where to go and where to stay. They do so only for our own good: health being the highest good, of course.
A recent edition of the New England Journal of Medicine discusses the issue in the context of the declaration of a public health emergency in Massachusetts by the governor of that state, Deval Patrick.
In most people’s minds, no doubt, a public health emergency would be something like the Black Death, the epidemic of plague that wiped out a third of Europe’s population in the fourteenth century. A natural disaster of large proportions might also count, not only because of the death and injury caused directly by the disaster, but by the epidemics which often follow such disasters.
What, then, was the public health emergency that “obliged” Patrick to declare that it existed and that he could and should take uncontrolled administrative measures to halt it?
When I visited the John F. Kennedy hospital in Monrovia during the long Liberian Civil War, it had been destroyed by a kind of conscientious vandalism. Every last piece of hospital furniture and equipment had been disabled, the wheels sawn off trolleys and gurneys, the electronics smashed. This was not just the result of bombardment during the war but of willful and thorough dismantlement.
There were no patients and no staff in the hospital; it was a ghost establishment, completely deserted. I was severely criticized for suggesting in a book that the painstaking destruction of the hospital, which shortly before had performed open heart surgery, was of symbolic significance.
I was pleased to see from an article in a recent edition of the New England Journal of Medicine that it had re-opened, but saddened to see that its problems were now of an even more terrifying nature than those it encountered during the civil war: for the hospital is at the center of the epidemic of Ebola virus disease, and two of its senior physicians, Sam Brisbane and Abraham Borbor, have recently died of it. The article in the journal lamented their passing and praised them for their bravery in not deserting their posts; they both knew of the dangers of refusing to do so.
Every few months I receive a computerized invitation from my doctor asking me to have a colonoscopy to screen for polyps in my bowel. I always tell myself that I am too busy just now, I will have it another time. But really I don’t want to have it at all, and I know that when the next invitation comes I will be too busy then as well.
I am also eager to find a rational reason, or at least a rationalization, for my refusal. I thought I found it in a paper from Norway in a recent edition of the New England Journal of Medicine.
The authors examined the death rate from colorectal cancer in Norway among the 40,826 patients between 1993 and 2007 who had had polyps removed at colonoscopy in that country (the records are more or less complete). They compared the number of deaths in that population with the expected death rate from the disease in the population the same age as a whole. The paper reports that 398 deaths were expected and 383 deaths were observed.
This small difference does not mean that colonoscopy does not work in preventing death from colorectal cancer, of course. This is because the relevant comparison is with people who had polyps not removed by colonoscopy rather than with the population as a whole.
The 40,826 patients who had polyps removed at colonoscopy, however, were not a random sample of the adult population because Norway does not have a screening program for colonic polyps. The patients had colonoscopy in the first place because they were symptomatic, for example bleeding per rectum. They were therefore much more likely to suffer from polyps or cancer in the first place than the rest of the population.
I happened to notice recently a report in a French newspaper of a study just published in the British Medical Journal, a study that had purportedly shown an increased incidence of cardiac death in people who took an antibiotic called clarithromycin. As I had myself taken this drug a couple of times in my life (though not, of course, quite as prescribed, because no one ever takes drugs quite as prescribed), I felt a certain personal interest in the question.
I needn’t have worried because the paper, from Denmark, claimed that the increased risk of cardiac death occurred only while the patient was taking the drug, not afterwards. But the closer I looked at the paper, the more darkness it seemed to shed on what doctors ought to do.
Denmark is a small country with a population of about 5.5 million, but it has the best health records in the world. This means that statisticians are able to churn out comparisons as Danish dairy farmers churn out butter.
The opening words of a novel are acknowledged to be among the most important of the book, my own favorite being Chesterton’s “The human race, to which so many of my readers belong.…” But rivaling these words for impact are those of the Methods section of the abstracts of two papers in a recent edition of the New England Journal of Medicine. The first was “We studied 102,216 adults from 18 countries,” surely the the equal of, say, “There was no possibility of going for a walk that day” (Jane Eyre). The second, by the same authors, was “We obtained morning fasting urine samples from 101,945 persons in 17 countries,” again easily the equal of “It was the best of times, it was the worst of times” (A Tale of Two Cities).
However, this was science, not literature. The object of the papers was to cast light on the association, long noted, between sodium intake in the diet and high blood pressure, and to help decide whether a reduction in the sodium intake of entire populations would be a worthwhile public health measure. High blood pressure is one of the principle causes of stroke and heart attack, which are themselves one of the principle causes of death in the world.
The dream of rejuvenating the aged by the infusion of young blood is much older than anyone living. It is said that the Scythians thought to make themselves strong by drinking the blood of their enemies killed in battle. And Dracula kept himself youthful by drinking the blood first of young maidens visiting Transylvania and later of maidens in England once he had moved there.
Blood is not the only tissue that has been thought to protect and rejuvenate the elderly. In the 1920s a Franco-Russian surgeon named Serge Voronoff transplanted monkey testes into men (some of them eminent, for example Kemal Ataturk) whose virility had declined, and claimed that it worked. He made a fortune but soon became the object of mockery and scorn, dying in prosperous obscurity in Switzerland in 1951.
There is always an air of charlatanry about those who claim to be able to turn the biological clock back (it is easy to find smooth-talking promoters of recaptured youth on the internet, for example), but a recent article in the New England Journal of Medicine suggests that some of the old ideas about the rejuvenating qualities of young blood may not have been quite so far-fetched after all. It is early days to proclaim that eternal youth is around the corner, and personally I am not sure I would want it even if it were, but according to the author a technique known as heterochronic parabiosis has retarded or reversed the aging process in mice. It is, of course, some distance from Mouse to Man.
What stands to reason is not always borne out by facts, for reality is often refractory to human wishes. There was a good illustration of this unfortunate principle in a recent edition of the New England Journal of Medicine.
It has long been known that low concentrations of high-density lipoproteins (HDL) and high concentrations of low-density lipoproteins (LDL) are associated, in a more or less linear fashion, with cardiovascular disease such as strokes and heart attacks. It would seem to stand to reason, therefore, that raising the HDL and lowering the LDL would lead to fewer cardiovascular “events,” as strokes and heart attacks are called.
One way to achieve this wished-for biochemical change is to treat patients at risk of such events with niacin, a B vitamin, in addition to the statins that they are already taking. The largest placebo-controlled trial of niacin ever undertaken, with 25,673 patients who had already had a stroke or heart attack, has shown that the addition of niacin, though it does indeed increase HDL and decrease LDL, has no effect on the rate of heart attack or stroke. Worse still, it gave rise to serious side effects, such as worsening of diabetes and unpleasant gastrointestinal, musculoskeletal and dermatological effects. One of the most unexpected findings of the trial was the excess of infections in people treated by niacin. If anything, the overall death rate in the niacin-treated group was higher than that in the placebo control group, though the difference was not statistically significant (which is not quite the same thing as saying that it was not real). The patients were followed up, on average, for nearly four years and at no time was treatment with niacin superior to that with placebo.
All medical journals these days feel the compulsion to be high-minded, but none is as high-minded as the Lancet. It is as if the editors had taken lessons both in moral philosophy and rhetoric from Mr. Pecksniff himself.
Mr. Pecksniff, you may remember, was the preposterous hypocrite in Dickens’ Martin Chuzzlewit, who introduces his daughters, Charity and Mercy, by adding “Not unholy names, I hope?” As Know thyself was inscribed over the entrance to the temple to Apollo at Delphi, and Abandon hope, all ye who enter here over the entrance to Dante’s hell, so Mr Pecksniff’s words, Let us be moral, must be inscribed over the entrance to the offices of the Lancet, figuratively if not literally
In the week before a Malaysian Airlines plane, taking many AIDS doctors and activists from Amsterdam to Melbourne for an international conference on AIDS, was shot down over eastern Ukraine, the Lancet published a statement called the Declaration of Melbourne, a typically sickly and nauseatingly unctuous statement of ethical principles. It began by saying something that, if not a lie exactly, was certainly not a truth:
We gather in Melbourne, the traditional meeting place of the Wurundjeri, Boonerwrung, Taungurong, Djajawurrung and the Wathaurung people, the original and enduring custodians of the lands that make up the Kulin Nation, to assess progress on the global HIV response and its future direction, at the 20th International AIDS Conference, AIDS 2014.
This, of course, is the purest 21st century Pecksniffery; and unless the signers of the declaration (who look extremely self-congratulatory in photos accompanying the article) can each and severally explain in what sense the Djajawarrung are the custodians of the lands on which the city of Melbourne is built, I suggest that they be banished to the outback for five years to live as pre-contact Australian Aborigines lived.
One of my first medical publications was on the nocebo effect, the unpleasant symptoms patients may suffer as a result of being made aware of potential side effects of a treatment they are about to receive or a procedure they are to undergo. Thus patients who were having a lumbar puncture were either told or not told they might suffer a headache afterwards; and lo and behold, those who were told that they might get headaches duly got headaches while those who were not told didn’t.
On the whole, as an article in a recent edition of the Journal of the American Medical Association points out, doctors are well aware of the placebo effect, that is to say the good that their treatment may do patients by means of mere suggestion, but have little awareness of the opposite nocebo effect, the harm that their treatment may do their patients by mere suggestion.
The nocebo effect poses an ethical dilemma for doctors, say authors of the article. On the one hand, doctors are supposed to do their patients no harm; on the other, they are supposed to be open and honest with their patients about the potential harms of drugs and other treatments. The dilemma is this: foreknowledge of those harms can harm some patients. Should the need for honesty trump the ethical injunction to do no harm?
Is there ever any good news without bad? Good and bad seem to be inextricably locked in a Hegelian dialectic, or perhaps Manichaean struggle would be a more accurate way of putting it. For example, tuberculosis became the captain of the men of death, the white plague, between the seventeenth and the nineteenth centuries. Then it began its long decline, accelerated by the discovery of the first effective anti-tuberculous drugs. Then, just as large numbers of people became more susceptible to tuberculosis because of the spread of the human immunodeficiency virus, the germ of tuberculosis developed resistance to the most effective drugs against it. It seemed that the disease might once more become what it had been not so very long before. But then, for the first time in 40 years, a new anti-tuberculous drug, bedaquiline, was developed by the pharmaceutical company Janssen. Good news has not retained the upper hand for very long, however. An article in a recent edition of the Lancet suggests that bedaquiline is not the answer to Mankind’s prayers, at least where tuberculosis is concerned.
The distinction between what the law permits and what the law enjoins is often blurred. An absence of proscription is sometimes mistaken for prescription. The more the law interferes in our lives, the more it becomes the arbiter of our morality. When someone behaves badly, therefore, he is nowadays likely to defend himself by saying that there is no law against what he has done, as if that were a sufficient justification.
The recent Supreme Court decision in the cases of Burwell v. Hobby Lobby Stores and Conestoga Wood Specialties Corp. v. Burwell illustrates the difficulties when two or more rights clash irreconcilably. The complex issues involved were the subject of an article in a recent edition of the New England Journal of Medicine. The matter is still far from settled. It seems to me likely that the Supreme Court will one day reverse itself when its philosophical (or ideological) composition has changed.
The two corporations were owned by strongly religious people. Corporations of their size were enjoined by the government to provide their staff with health insurance which would cover contraceptive services. However, some contraceptive methods violated the religious beliefs of the owners of the companies. Did the companies have the right to except these methods from the policies that they offered to their staff (who, incidentally, numbered thousands, many of whom would not be of the same religious belief)?
In principle medical research is supposed to result in unequivocal guidance to doctors as to how to treat their patients. As often as not, however, the waters are muddied as much as cleared. Two papers in a recent edition of the New England Journal of Medicine about atrial fibrillation and the cause of stroke illustrate this. It has long been known that people with a clinically-detected chaotic heart rhythm called atrial fibrillation (AF) have an increased incidence of stroke by embolism; and likewise that no cause of such stroke can be found in up to 40 percent of patients who suffer from one. Their strokes are called cryptogenic. The two papers addressed the question whether, if you monitor patients with cryptogenic stroke for long enough, some or many of them will turn out to suffer from AF. This is important, because it is generally agreed that, in patients with clinically detected and symptomatic AF, anti-coagulation reduces the subsequent risk of stroke. AF, however, is not an all or none phenomenon. Some people suffer it continuously, but others only occasionally and for only a few seconds at a time. The additional risk of stroke in the latter is unknown, but is an important question because the anticoagulation designed to reduce the risk of stroke is not itself without risk, including that of another kind of stroke, the haemorrhagic kind. In other words, the risk caused by treatment could outweigh its benefits.
If the future were knowable, would we want to know it? When I was young, a fortune teller who predicted several things in my life that subsequently came true predicted my age at death. At the time it seemed an eternity away, so I thought no more of it, but now it is not so very long away at all. If I were more disposed to believe the fortune teller’s prediction than I am, would I use my remaining years more productively or would I be paralyzed with fear?
In a recent edition of the New England Journal of Medicine a question was posed about a 45-year-old man in perfect health (insofar as health can ever be described as perfect) who asked for genetic testing about his susceptibility to cancer, given a fairly strong family history of it. Should he have his genome sequenced?
A geneticist answered that he should not: to have his entire genome sequenced would lead to a great deal of irrelevant and possibly misleading information. But if the family history were of cancers that themselves were of the partially inherited type – more factors than genetics are involved in the development of most cancers – then the man might well consider having the relevant part of his genome, namely that part with a known predisposing connection to the cancers from which his family had suffered, sequenced.
This is not a complete answer, however. Two obvious questions arise: is additional risk clinically as well as statistically significant, and if the risk is known can anything practicable and tolerable be done to reduce it? There is no point in avoiding a risk if to do so makes your life a misery in other respects. You can avoid the risk altogether of a road traffic accident or being mugged on the street by never leaving your house, but few people would recommend such drastic avoidance.
Pressure to control the consumption of tobacco has grown in tandem with the pressure to liberalize the consumption of marijuana. Perhaps this is not a paradox in the most literal sense, but it is certainly very striking. The yin of prohibition, it seems, always goes along with the yang of permission.
An article in a recent edition of the New England Journal of Medicine discusses the forthcoming tussle between what it calls Big Marijuana – the commercial interests, analogous to Big Tobacco, that will inevitably grow if marijuana ever becomes as accepted as tobacco once was – and the public health authorities. For while the smoking of marijuana does not yet cause anything like as many health problems as tobacco or alcohol, it would do so if its use were as general as the use of tobacco or alcohol. A little statistic that was published some time ago in the Lancet caught my eye: the French police attribute 3 percent of fatal road accidents to intoxication with cannabis and 30 percent to intoxication with alcohol. If, as seems likely, ten times as many Frenchmen drive drunk as drive stoned, marijuana is as dangerous as alcohol where driving is concerned.
The authors of the article point out that commercial growers and marketers of marijuana are likely, given the chance, to resort to all the techniques and obfuscations employed by the tobacco companies. They will minimize the harms done by marijuana while trying to increase the concentration of the very substance in their product that does the harm. The concentration of tetrahydrocannabinol (THC) in modern cannabis plants is already much higher than it was when hippiedom first struck the western world; Uruguay, where the cultivation and sale of cannabis has recently been legalized, is attempting to control the strains of cannabis that can be sold, with what success remains to be seen.
As long as men have experimented upon animals to gain knowledge of physiology or pathology there have been others who have decried the practice. Among them was Doctor Johnson, who said of vivisection that “if the knowledge of physiology has been somewhat increased [by it], he surely buys knowledge dear, who learns the use of lacteals at the expense of his humanity.”
Doctor Johnson argued that the cure of not a single medical condition had been discovered by the use of animal experimentation, and even if that is no longer the case there are nevertheless those who maintain that the benefits of animal research are small by comparison with their cost in the suffering of sentient beings that such research entails.
Two authors in a recent edition of the British Medical Journal, one of them an eminent epidemiologist and the other a sociologist, attempt to answer the question of whether or not animal research is a boon to medicine. Their conclusion is that it is much less so than is commonly supposed, and in some cases it is actually harmful. Since the only possible moral defense of vivisection is that it promotes medical advance, it should be stopped if it does not.
The authors point out that, according to a survey of medical scientists who perform animal experimentation, more are motivated by a desire to advance knowledge or careers than by a desire to help suffering humanity, and are actually rather indifferent to the practical use or otherwise of their work.
This is perhaps just as well, at least for their own peace of mind, because the practical value to patients of most animal experimentation is nil. This is for more than one reason.
Internet discussions usually descend into abuse within a few postings. Whether this is because people these days are less polite and restrained than they used to be, or because the internet allows them to publish their first reactions without the time to cool off that older means of communication entailed, I do not know; but the fact is that those who take part in such discussions seem to confuse insult with argument and are seldom able to keep to the point for very long.
Doctors, if the internet discussions that follow articles that appear in the New England Journal of Medicine are anything to go by, are better than average. Often, indeed, though not always, they employ rational argument. Perhaps there is something to be said after all for a long and rigorous education.
Not long ago there appeared an article in the NEJM throwing doubt on the wisdom and even the ethics of screening by mammography for early cancer of the breast. A Swiss commission examined the evidence for the benefits and found none, or some so slight that it hardly counted. The best estimate they could come up with was that mammography saved one life from breast cancer per 1000 women aged 50 who underwent screening, but that the all-cause death rate in the screened and unscreened was practically the same. Not only did many screened women undergo unnecessary operations and much radiotherapy for false positive results, but those who offered the screening were little more honest than second-hand car salesmen, in effect preying on the women’s complete misunderstanding of the supposed benefits of screening. Women believe that even with screening they are twenty times more likely to die of the disease than in fact they are; and they overestimate the benefits of screening by eighty times.
In the circumstances, then, the Swiss panel suggested that screening by mammography should be stopped forthwith.
Shortness of breath is a very unpleasant sensation and people with chronic obstructive pulmonary disease (COPD) have it chronically. It is not something that you can ever get used to, breath being so essential to life, and the disease worsens relentlessly; without medical attention one dies slowly of suffocation. That is a horrible way to die. Though COPD will become less common in time, thanks to a reduction in smoking (except in Colorado), it is still the third most common cause of death among adults in America.
As yet there is no cure and perhaps there will never be one, short of lung transplant; but it has been reported many times in the medical press that statins, drugs taken to reduce the risk of heart attack among the otherwise susceptible, ameliorate the symptoms and reduce the frequency of acute exacerbations.
Patients who have COPD and are taking statin drugs to reduce their risk of heart attack or stroke have been thought to experience fewer acute exacerbations of the disease and as a consequence to live longer. There is biological plausibility to this observation, for statins have an anti-inflammatory effect and exacerbations of COPD are caused by infection and its consequent inflammation.
If a Martian were to land on earth to study humanity, one of the things that would no doubt surprise him about our race is the pleasure it takes in contemplating its own extinction by various catastrophic means: the crash into earth of a giant asteroid, climate change or the spread of new, virulent and untreatable diseases, especially caused by viruses that emerged from the African jungle.
Of all the viruses to have emerged of late, Ebola is the most frightening. It comes in several varieties of different virulence, with (according to a recent article in the New England Journal of Medicine) death rates from a “low” 40 percent to over 70 percent. Among monkeys the death rate can be 100 percent.
Before Ebola there was Marburg, so named because it was first recognized among laboratory workers in Marburg, Germany. This virus is spread from fruit bats to monkeys to humans, and I happened to be in Rhodesia (as it was then still called) when there was an epidemic there of the disease and 33 percent of the patients died. I remember the reaction in the hospital between panic and pride that it should be in the eye of a world-publicized storm. The question on everyone’s mind was whether it could spread on a large scale from Africa to Europe and North America. Could the virus escape its ecological niche?
I remember the written response of the senior doctor in the prison in which I worked to an editorial in the British Medical Journal lamenting the difference between health care in prison and health care in the “community.” Yes, he replied, where else in the country but in prison could everyone get to see a doctor within an hour of complaining of something?
I thought of this as I read an article recently in the New England Journal of Medicine about Hepatitis C infection and the American correctional system.
About 3 million Americans are infected with the Hepatitis C virus, mainly because of having shared needles in intravenous drug abuse, but also through transfusions before blood was screened for the virus. Those who are tattooed have two or three times the average rate of infection.
Ten-to-fifteen percent of cases of untreated infection (among males) will go on to get cirrhosis of the liver, and of them an increasing proportion will develop liver cancer as the years go by. Hepatitis C infection is now the largest single cause of the need for liver transplants.
Sometimes the New England Journal of Medicine reads like a journal of failed bright ideas. I do not remember ever having read of so many failed trials of treatment as I have recently, but perhaps that is a sign of increasing scientific honesty. After all, it is as important to know what does not work as what does, especially when what does not work is very expensive to administer.
Septic shock is a condition of dangerously low blood pressure brought about by serious infection. About 750,000 cases a year are treated in the United States alone, with a death rate above 20 percent, that is to say at least 150,000 people die of it each year. This is a number well worth reducing.
More than a decade ago the results of a trial were published in which it was shown that aggressive treatment according to a pre-arrange protocol could reduce the death rate from septic shock by about a half. In those days (medicine 10 years ago seems that of a bygone era), the death rate in septic shock was much higher than it is today, which may in part explain the success of that trial compared with the failure of a more recent trial published recently in the NEJM.